Dietary fatty acids modulate chronic colitis, colitis-associated colon neoplasia and COX-2 expression in IL-10 knockout mice

Hegazi, Refaat; Saad, Reda S.; Mady, Hussam H.; Matarese, Laura E.; O’Keefe, Stephen J.; Kandil, Hossam M.

doi:10.1016/j.nut.2005.06.006

Cited by 61 publications

(64 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…COX-2 expression is increased in most active human IBD samples (40) and in mouse models of IBD (41). Therefore, we immunostained p120 control and KO tissues with antibodies to COX-2.…”

Section: Figurementioning

confidence: 99%

“…Interestingly, it has been reported that p120 is locally downregulated in 100% of active ulcerative colitis cases and 75% of active Crohn disease cases (53), the former being strongly associated with predisposition to colon cancer (i.e., colitis-associated cancer) (41). In addition, Kucharzik et al have shown in IBD patients that E-cadherin and β-catenin are locally reduced in neutrophil-containing crypt abscesses but not in uninvolved areas (i.e., neutrophil negative), a result consistent with transient downregulation of p120 (54).…”

Section: Figurementioning

confidence: 99%

“…Of note, most neutrophils in the p120 KO colon were also COX-2 positive. Elevated COX-2 activity is thought to play an important role in both IBD and colon cancer (41,43,44), but the source of the activity is controversial. Elevated COX-2 has been reported variously in epithelial cells, as well as almost every stromal cell type (44, 64) -macrophages in particular (65).…”

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

p120-catenin is essential for maintenance of barrier function and intestinal homeostasis in mice

Smalley-Freed¹,

Ефимов²,

Burnett³

et al. 2010

J. Clin. Invest.

123

152

View full text Add to dashboard Cite

Epithelial-cadherin (E-cadherin) is a master organizer of the epithelial phenotype. Its function is regulated in part by p120-catenin (referred to herein as p120), a cytoplasmic binding partner that directly regulates cadherin stability. As it has been suggested that cadherins have a role in inflammatory bowel disease (IBD), we sought to investigate this further by assessing the effect of p120 deficiency in mouse small intestine and colon. p120 conditional KO mice were superficially normal at birth but declined rapidly and died within 21 days. Cellcell adhesion defects and inflammation led to progressive mucosal erosion and terminal bleeding, similar to what is observed in a dominant-negative cadherin mouse model of IBD. Additionally, selective loss of adherens junctions and accumulation of atypical COX-2-expressing neutrophils in p120-null areas of the colon were observed. To elucidate the mechanism, direct effects of p120 deficiency were assessed in vitro in a polarizing colon cancer cell line. Notably, transepithelial electrical resistance was dramatically reduced, neutrophil binding was increased 30 fold, and levels of COX-2, an enzyme associated with IBD, were markedly increased in neutrophils. Our data suggest that p120 loss disrupts the neonatal intestinal barrier and amplifies neutrophil engagement and that these changes lead to catastrophic inflammation during colonization of the neonatal gut with bacteria and other luminal antigens. Thus, we conclude that p120 has an essential role in barrier function and epithelial homeostasis and survival in the intestine.

show abstract

“…COX-2 expression is increased in most active human IBD samples (40) and in mouse models of IBD (41). Therefore, we immunostained p120 control and KO tissues with antibodies to COX-2.…”

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

See 1 more Smart Citation

p120-catenin is essential for maintenance of barrier function and intestinal homeostasis in mice

Smalley-Freed¹,

Ефимов²,

Burnett³

et al. 2010

J. Clin. Invest.

123

152

View full text Add to dashboard Cite

show abstract

“…IL-10 is considered an immunoregulatory cytokine which exerts effects in both the innate immune response and in the adaptive immune response. IL-10 Knochout animals, for example, develop colitis spontaneously, and 30 to 60% of these animals show invasive carcinoma of the colon between 3 and 6 months of age (Hegazi et al 2006. These animals have two important characteristics: 1) an increased intestinal permeability in an early age, and before the onset of the disease; 2) the development of colitis, dependent on the microbiological presence in the intestinal lumen.…”

Section: Inflammatory Bowel Disease and Dietary Fatty Acidsmentioning

confidence: 99%

“…Some studies have demonstrated the role of IL-10 on gastrointestinal mucosal homeostasis maintenance. The mechanism by which this cytokine regulates mucosal inflammation is probably multifactorial; however, it is associated with reduced antigen presentation (Hegazi et al 2006, an increased release of IFN-and IL-12 -a cytokine that inhibits the differentiation of T lymphocytes into Th1 lymphocytes (Rennick & Fort 2000). There is strong evidence that IL-10 promotes the differentiation and the increase of the activity of the regulatory T cells (Hegazi et al 2006).…”

Section: Inflammatory Bowel Disease and Dietary Fatty Acidsmentioning

confidence: 99%

Polyunsaturated Fatty Acids, Ulcerative Colitis and Cancer Prevention

Barros¹,

Cassulino²,

Silveira³

2012

Colorectal Cancer - From Prevention to Patient Care

View full text Add to dashboard Cite

Long non‐coding RNA cox‐2 prevents immune evasion and metastasis of hepatocellular carcinoma by altering M1/M2 macrophage polarization

Lai

et al. 2017

J of Cellular Biochemistry

175

143

View full text Add to dashboard Cite

Macrophages have been shown to demonstrate a high level of plasticity, with the ability to undergo dynamic transition between M1 and M2 polarized phenotypes. We investigate long non-coding RNA (lncRNA) cox-2 in macrophage polarization and the regulatory mechanism functions in hepatocellular carcinoma (HCC). Lipopolysaccharide (LPS) was used to induce RAW264.7 macrophages into M1 type, and IL-4 was to induce RAW264.7 macrophages into M2 type. We selected mouse hepatic cell line Hepal-6 and hepatoma cell line HepG2 for co-incubation with M1 or M2 macrophages. Quantitative real-time PCR was used to detect the expressions of lncRNA cox-2 and mRNAs. ELISA was conducted for testing IL-12 and IL-10 expressions; Western blotting for epithelial mesenchymal transition related factors (E-cadherin and Vimentin). An MTT, colony formation assay, flow cytometry, transwell assay, and stretch test were conducted to test cell abilities. The M1 macrophages had higher lncRNA cox-2 expression than that in the non-polarized macrophages and M2 macrophages. The lncRNA cox-2 siRNA decreased the expression levels of IL-12, iNOS, and TNF-α in M1 macrophages, increased the expression levels of IL-10, Arg-1, and Fizz-1 in M2 macrophages (all P < 0.05). The lncRNA cox-2 siRNA reduces the ability of M1 macrophages to inhibit HCC cell proliferation, invasion, migration, EMT, angiogenesis and facilitate apoptosis while strengthening the ability of M2 macrophages to promote proliferation HCC cell growth and inhibit apoptosis. These findings indicate that lncRNA cox-2 inhibits HCC immune evasion and tumor growth by inhibiting the polarization of M2 macrophages.

show abstract

Dietary fatty acids modulate chronic colitis, colitis-associated colon neoplasia and COX-2 expression in IL-10 knockout mice

Cited by 61 publications

References 38 publications

p120-catenin is essential for maintenance of barrier function and intestinal homeostasis in mice

p120-catenin is essential for maintenance of barrier function and intestinal homeostasis in mice

Polyunsaturated Fatty Acids, Ulcerative Colitis and Cancer Prevention

Long non‐coding RNA cox‐2 prevents immune evasion and metastasis of hepatocellular carcinoma by altering M1/M2 macrophage polarization

Contact Info

Product

Resources

About